Immunohistochemical evaluation of keratins and involucrin in differentiating between palmoplantar pustulosis and pompholyx.

BACKGROUND: Palmoplantar pustulosis (PPP) and pompholyx are chronic diseases characterized by pustules and vesicles on the palms and soles. These disorders often have similar clinicopathological features, which lead to diagnostic difficulties. We aimed to investigate the expression patterns of keratins and involucrin in PPP and pompholyx using immunohistochemical staining. METHODS: Skin biopsies from patients with PPP (n = 40) and pompholyx (n = 22) were immunohistochemically analyzed for Keratin 5, 9, 14, and involucrin expression. RESULTS: K5 expression was higher in PPP than in pompholyx, with diffusely positive expression in the basal, spinous, and granular layers. K14 expression did not differ between groups. K9 expression was observed near the pompholyx vesicle (P = 0.014) and stratum spinosum (P < 0.001) but was almost absent around PPP pustules. Involucrin expression was diffused around the PPP pustules and partially around the pompholyx vesicles, but without statistical significance (P = 0.123). Involucrin expression was elevated in the basal layer of the PPP compared with that in the pompholyx (P = 0.023). CONCLUSION: PPP and pompholyx exhibited distinctive differentiation in the expression of K5, K9, and involucrin.

Multiphysics Modeling Framework for Soft PVC Gel Sensors with Experimental Comparisons.

Polyvinyl chloride (PVC) gels have recently been found to exhibit mechanoelectrical transduction or sensing capabilities under compressive loading applications. This phenomenon is not wholly understood but has been characterized as an adsorption-like phenomena under varying amounts and types of plasticizers. A different polymer lattice structure has also been tested, thermoplastic polyurethane, which showed similar sensing characteristics. This study examines mechanical and electrical properties of these gel sensors and proposes a mathematical framework of the underlying mechanisms of mechanoelectrical transduction. COMSOL Multiphysics is used to show solid mechanics characteristics, electrostatic properties, and transport of interstitial plasticizer under compressive loading applications. The solid mechanics takes a continuum mechanics approach and includes a highly compressive Storakers material model for compressive loading applications. The electrostatics and transport properties include charge conservation and a Langmuir adsorption migration model with variable diffusion properties based on plasticizer properties. Results show both plasticizer concentration gradient as well as expected voltage response under varying amounts and types of plasticizers. Experimental work is also completed to show agreeance with the modeling results.

On the mechanism of performance improvement of electroactive polyvinyl chloride (PVC) gel actuators via conductive fillers.

The electromechanical actuation of transparent plasticized polyvinyl chloride (PVC) gels with conductive fillers were studied. The effects of functionalized carbon nanotubes (CNTs) and 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF4) ionic liquid (IL) on both the electrical conduction and dielectric processes within PVC gels were investigated, and the differences between the two were clarified. Both CNTs and IL were shown to increase the conductivity of the gels and produce larger electromechanical transduction of a contraction actuator, but only CNTs were shown to increase the electrostatic adhesion force of the PVC gels. The addition of charge carriers to the gel via the inclusion of ILs was shown to significantly reduce the conductivity relaxation time, and the transient current upon voltage polarity reversal indicated multiple peaks corresponding to the introduction of carriers with different polarities and mobilities into the gel. This is believed to cause a screening effect, reducing the charge accumulation at the anode that is the foundational basis for PVC gels' actuation mechanism. A recommendation for preferable conductive fillers for various applications is made.

Effects of Urban Particulate Matter on the Olfactory System in a Mouse Model.

BACKGROUND: Exposure to urban particulate matter (UPM) is linked to the aggravation of various health problems. Although the nasal cavity is the first barrier to encounter UPM, there is a lack of studies on the impact of UPM on the olfactory area. The purpose of this study was to investigate the cytotoxic effects of UPM on mouse olfactory epithelium, the underlying pathophysiology involved, and changes in cytokine levels. METHODS: Mice were divided into 4 groups: control, 400UPM (administered 400 µg UPM daily; standard reference material 1649b; average particle diameter 10.5 µm) 1week, 400UPM 2weeks, and recovery 1week after 400UPM 2weeks (n = 10, 6, 6, and 6, respectively). Olfactory function was evaluated by conducting a food-finding test once a week. The olfactory neuroepithelium was harvested for histologic examination, gene ontology, quantitative real-time polymerase chain reaction, and western blotting. RESULTS: Compared to those in the control group, olfactory marker protein, olfactory receptor 1507, adenylyl cyclase 3, and GNAL mRNA levels were lower and S-100, 2',3'-cyclic nucleotide 30-phosphodiesterase, nerve growth factor receptor-associated protein, brain-derived neurotrophic factor, and tachykinin receptor mRNA levels were higher in the 400UPM group olfactory neuroepithelium. There were no significant differences in neuroepithelial inflammatory marker levels between the 400UPM and saline group. CONCLUSIONS: UPM decreased olfactory function and might have cytotoxic effects on the olfactory epithelium. Olfactory ensheathing cells and trigeminal nerve might be related to the regeneration of the olfactory epithelium after olfactory destruction associated with UPM.

Author Correction: Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation.

A Correction to this paper has been published: https://doi.org/10.1038/s41551-021-00725-w.

111In-Oxine-WBC SPECT/CT of Lumbosacral Facet Joint Septic Arthritis.

Spinal facet joint septic arthritis is a rare pathology associated with pyogenic organisms. It may present in older adults with back pain, fever, and positive bacterial blood cultures. However, clinical presentation may be equivocal, and diagnosis relies on anatomic imaging for differentiation from other pathologies. Magnetic resonance is considered the imaging modality of choice and has been found superior to CT; however, it is unable to differentiate facet joint septic arthritis from other inflammatory arthropathies. We present a case of lumbosacral facet joint septic arthritis as seen on In-oxine-WBC scintigraphy and SPECT/CT.

Brain perfusion single-photon emission computerized tomography/computerized tomography: Stroke-like manifestations of COVID-19 with transient antiphospholipid elevation.

COVID-19 is a viral respiratory disease associated with neurologic complications such as encephalitis or stroke in a minority of patients. The wide variety of neurologic manifestations with often unclear etiology may confound diagnosis and management. We present a young man admitted following an 8-day onset of self-resolving episodes of left hemiplegia and hemifacial droop. Diagnostic work up for seizures and stroke was largely negative. "Intra-ictal" ECD-single-photon emission computerized tomography/computerized tomography was consistent with right middle cerebral artery ischemia. Subsequent diagnostic work up revealed positive COVID-19 screening and newly-elevated antiphospholipid antibodies. Antiepileptic medications were discontinued, and the patient was successfully treated as an outpatient with corticosteroids leading to resolution of symptoms.

Advanced Resistance Studies Identify Two Discrete Mechanisms in Staphylococcus aureus to Overcome Antibacterial Compounds that Target Biotin Protein Ligase.

Biotin protein ligase (BPL) inhibitors are a novel class of antibacterial that target clinically important methicillin-resistant Staphylococcus aureus (S. aureus). In S. aureus, BPL is a bifunctional protein responsible for enzymatic biotinylation of two biotin-dependent enzymes, as well as serving as a transcriptional repressor that controls biotin synthesis and import. In this report, we investigate the mechanisms of action and resistance for a potent anti-BPL, an antibacterial compound, biotinyl-acylsulfamide adenosine (BASA). We show that BASA acts by both inhibiting the enzymatic activity of BPL in vitro, as well as functioning as a transcription co-repressor. A low spontaneous resistance rate was measured for the compound (<10-9) and whole-genome sequencing of strains evolved during serial passaging in the presence of BASA identified two discrete resistance mechanisms. In the first, deletion of the biotin-dependent enzyme pyruvate carboxylase is proposed to prioritize the utilization of bioavailable biotin for the essential enzyme acetyl-CoA carboxylase. In the second, a D200E missense mutation in BPL reduced DNA binding in vitro and transcriptional repression in vivo. We propose that this second resistance mechanism promotes bioavailability of biotin by derepressing its synthesis and import, such that free biotin may outcompete the inhibitor for binding BPL. This study provides new insights into the molecular mechanisms governing antibacterial activity and resistance of BPL inhibitors in S. aureus.

Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation.

Exosomes are attractive as nucleic-acid carriers because of their favourable pharmacokinetic and immunological properties and their ability to penetrate physiological barriers that are impermeable to synthetic drug-delivery vehicles. However, inserting exogenous nucleic acids, especially large messenger RNAs, into cell-secreted exosomes leads to low yields. Here we report a cellular-nanoporation method for the production of large quantities of exosomes containing therapeutic mRNAs and targeting peptides. We transfected various source cells with plasmid DNAs and stimulated the cells with a focal and transient electrical stimulus that promotes the release of exosomes carrying transcribed mRNAs and targeting peptides. Compared with bulk electroporation and other exosome-production strategies, cellular nanoporation produced up to 50-fold more exosomes and a more than 103-fold increase in exosomal mRNA transcripts, even from cells with low basal levels of exosome secretion. In orthotopic phosphatase and tensin homologue (PTEN)-deficient glioma mouse models, mRNA-containing exosomes restored tumour-suppressor function, enhanced inhibition of tumour growth and increased survival. Cellular nanoporation may enable the use of exosomes as a universal nucleic-acid carrier for applications requiring transcriptional manipulation.

The formation of perianchor fluid associated with various suture anchors used in rotator cuff repair: all-suture, polyetheretherketone, and biocomposite anchors.

AIMS: The aim of this study was to compare the osseous reactions elicited by all-suture, polyetheretherketone (PEEK), and two different biodegradable anchors used during rotator cuff repair. PATIENTS AND METHODS: Transosseous-equivalent rotator cuff repair was performed in 73 patients. The patients were divided into two groups, in both of which two different medial-row anchors were used. In group 1, anchor A comprised 30% ß-tricalcium phosphate (TCP) + 70% fast-absorbing poly lactic-co-glycolic acid copolymer (85% polylactic acid enantiomers + 15% polyglycolic acid) and anchor B comprised all-sutures. In group 2, anchor C comprised 23% micro ß-TCP + 77% polylactic acid enantiomers and anchor D comprised PEEK polymer. There were 37 patients in group 1 and 36 patients in group 2. The presence and severity of fluid collection around anchors and healing of the rotator cuff were assessed using MRI scans, approximately one year postoperatively. The severity of the collection was graded as 0 (no perianchor fluid signal), 1 (minimal perianchor fluid), 2 (local collection of fluid), 3 (fluid collection around the whole length of the anchor but of a diameter less than twice the anchor diameter), or 4 (fluid collection around the whole length of the anchor and of a diameter greater than twice the anchor diameter). RESULTS: A perianchor fluid signal was seen in three patients (8.1%) with anchor A, four (10.8%) with anchor B, 15 (41.7%) with anchor C, and 15 (41.7%) with anchor D. The severity of the collection around anchor was grade 2:1:0:0 for anchor A, grade 2:2:0:0 for anchor B, grade 12:2:0:1 for anchor C, and grade 11:3:0:1 for anchor D (grade 1:2:3:4, respectively). The prevalence and severity of fluid formation was not significantly different between anchors A and B, and anchors C and D. However, on intergroup analysis, there were significant differences for the prevalence and severity of fluid formation between anchors in group 1 and group 2. The prevalence of failure to heal was not significant in group 1 (seven, 18.9%) or group 2 (nine, 25.0%). There was no relationship between the presence of perianchor fluid and each type of anchor, and the integrity of the rotator cuff repair, in either group. CONCLUSION: Despite the nonabsorbable nature of all-suture and PEEK anchors, all-suture anchors produced less osseous reaction after rotator cuff repair. In deciding which kind of anchor to use, consideration should be given not only to the strength of the initial fixation, but also to the postoperative biological reaction. Cite this article: Bone Joint J 2019;101-B:1506-1511.

3D-Printing and Machine Learning Control of Soft Ionic Polymer-Metal Composite Actuators.

This paper presents a new manufacturing and control paradigm for developing soft ionic polymer-metal composite (IPMC) actuators for soft robotics applications. First, an additive manufacturing method that exploits the fused-filament (3D printing) process is described to overcome challenges with existing methods of creating custom-shaped IPMC actuators. By working with ionomeric precursor material, the 3D-printing process enables the creation of 3D monolithic IPMC devices where ultimately integrated sensors and actuators can be achieved. Second, Bayesian optimization is used as a learning-based control approach to help mitigate complex time-varying dynamic effects in 3D-printed actuators. This approach overcomes the challenges with existing methods where complex models or continuous sensor feedback are needed. The manufacturing and control paradigm is applied to create and control the behavior of example actuators, and subsequently the actuator components are combined to create an example modular reconfigurable IPMC soft crawling robot to demonstrate feasibility. Two hypotheses related to the effectiveness of the machine-learning process are tested. Results show enhancement of actuator performance through machine learning, and the proof-of-concepts can be leveraged for continued advancement of more complex IPMC devices. Emerging challenges are also highlighted.

Design and Modeling of a New Biomimetic Soft Robotic Jellyfish Using IPMC-Based Electroactive Polymers.

Smart materials and soft robotics have been seen to be particularly well-suited for developing biomimetic devices and are active fields of research. In this study, the design and modeling of a new biomimetic soft robot is described. Initial work was made in the modeling of a biomimetic robot based on the locomotion and kinematics of jellyfish. Modifications were made to the governing equations for jellyfish locomotion that accounted for geometric differences between biology and the robotic design. In particular, the capability of the model to account for the mass and geometry of the robot design has been added for better flexibility in the model setup. A simple geometrically defined model is developed and used to show the feasibility of a proposed biomimetic robot under a prescribed geometric deformation to the robot structure. A more robust mechanics model is then developed which uses linear beam theory is coupled to an equivalent circuit model to simulate actuation of the robot with ionic polymer-metal composite (IPMC) actuators. The mechanics model of the soft robot is compared to that of the geometric model as well as biological jellyfish swimming to highlight its improved efficiency. The design models are characterized against a biological jellyfish model in terms of propulsive efficiency. Using the mechanics model, the locomotive energetics as modeled in literature on biological jellyfish are explored. Locomotive efficiency and cost as a function of swimming cycles are examined for various swimming modes developed, followed by an analysis of the initial transient and steady-state swimming velocities. Applications for fluid pumping or thrust vectoring utilizing the same basic robot design are also proposed. The new design shows a clear advantage over its purely biological counterpart for a soft-robot, with the newly proposed biomimetic swimming mode offering enhanced swimming efficiency and steady-state velocities for a given size and volume exchange.

Understanding the Thermal Properties of Precursor-Ionomers to Optimize Fabrication Processes for Ionic Polymer-Metal Composites (IPMCs).

Ionic polymer-metal composites (IPMCs) are one of many smart materials and have ionomer bases with a noble metal plated on the surface. The ionomer is usually Nafion, but recently Aquivion has been shown to be a promising alternative. Ionomers are available in the form of precursor pellets. This is an un-activated form that is able to melt, unlike the activated form. However, there is little study on the thermal characteristics of these precursor ionomers. This lack of knowledge causes issues when trying to fabricate ionomer shapes using methods such as extrusion, hot-pressing, and more recently, injection molding and 3D printing. To understand the two precursor-ionomers, a set of tests were conducted to measure the thermal degradation temperature, viscosity, melting temperature, and glass transition. The results have shown that the precursor Aquivion has a higher melting temperature (240 °C) than precursor Nafion (200 °C) and a larger glass transition range (32⁻65°C compared with 21⁻45 °C). The two have the same thermal degradation temperature (~400 °C). Precursor Aquivion is more viscous than precursor Nafion as temperature increases. Based on the results gathered, it seems that the precursor Aquivion is more stable as temperature increases, facilitating the manufacturing processes. This paper presents the data collected to assist researchers in thermal-based fabrication processes.

Mechanical properties and cytotoxicity of PLA/PCL films.

Thermodynamically immiscible poly(lactic acid) (PLA) and poly(ε-caprolactone) (PCL) were blended and solution-cast by adding the 3% compatibilizer (tributyl citrate, TBC) of the PCL weight. In the PLA/PCL composition range of 99/1-95/5 wt%, mechanical properties of the PLA/PCL films with TBC were always superior to those of the films without TBC. The tensile strength of 42.9 ± 3.5 MPa and the elongation at break of 10.3 ± 2.7% were observed for the 93/7 PLA/PCL films without TBC, indicating that PCL addition is effective for strength and ductility. However, the tensile strength of 54.1 ± 3.4 MPa and the elongation at break of 8.8 ± 1.8% were found for the 95/5 PLA/PCL with TBC, indicating that the effect of co-addition of PCL and TBC on mechanical properties of the films is more pronounced. No cytotoxicity was observed for the PLA/PCL films regardless of TBC addition.

Mechanical properties and cytotoxicity of PLA/PCL films

Thermodynamically immiscible poly(lactic acid) (PLA) and poly(ε-caprolactone) (PCL) were blended and solution-cast by adding the 3% compatibilizer (tributyl citrate, TBC) of the PCL weight. In the PLA/PCL composition range of 99/1–95/5 wt%, mechanical properties of the PLA/PCL films with TBC were always superior to those of the films without TBC. The tensile strength of 42.9 ± 3.5 MPa and the elongation at break of 10.3 ± 2.7% were observed for the 93/7 PLA/PCL films without TBC, indicating that PCL addition is effective for strength and ductility. However, the tensile strength of 54.1 ± 3.4 MPa and the elongation at break of 8.8 ± 1.8% were found for the 95/5 PLA/PCL with TBC, indicating that the effect of co-addition of PCL and TBC on mechanical properties of the films is more pronounced. No cytotoxicity was observed for the PLA/PCL films regardless of TBC addition.

The Leukocyte Esterase Strip Test has Practical Value for Diagnosing Periprosthetic Joint Infection After Total Knee Arthroplasty: A Multicenter Study.

BACKGROUND: Leukocyte esterase (LE) was recently reported to be an accurate marker for diagnosing periprosthetic joint infection (PJI) as defined by the Musculoskeletal Infection Society (MSIS) criteria. However, the diagnostic value of the LE test for PJI after total knee arthroplasty (TKA), the reliability of the subjective visual interpretation of the LE test, and the correlation between the LE test results and the current MSIS criteria remain unclear. METHODS: This study prospectively enrolled 60 patients undergoing revision TKA for either PJI or aseptic failure. Serological marker, synovial fluid, and histological analyses were performed in all cases. The PJI group comprised 38 cases that met the MSIS criteria and the other 22 cases formed the aseptic group. All the LE tests were interpreted using both visual judgment and automated colorimetric reader. RESULTS: When "++" results were considered to indicate a positive PJI, the sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were 84, 100, 100, 79, and 90%, respectively. The visual interpretation agreed with the automated colorimetric reader in 90% of cases (Cronbach α = 0.894). The grade of the LE test was strongly correlated with the synovial white blood cell count (ρ = 0.695) and polymorphonuclear leukocyte percentage (ρ = 0.638) and moderately correlated with the serum C-reactive protein and erythrocyte sedimentation rate. CONCLUSION: The LE test has high diagnostic value for diagnosing PJI after TKA. Subjective visual interpretation of the LE test was reliable and valid for the current battery of PJI diagnostic tests according to the MSIS criteria.

False-Positive Ventilation-Perfusion Studies Due to Nonembolic Pulmonary Artery Compromise.

Ventilation/perfusion (V/Q) scans are highly sensitive in detecting clinically significant pulmonary embolisms; however, V/Q mismatches are not specific to pulmonary embolism alone, and other etiologies can cause false-positive results. We present 3 cases where the pulmonary vasculature was compromised, from either intraluminal narrowing or external compression, with resultant mismatches. This raises the importance of interpreting V/Q scan results in conjunction with a thorough medical/surgical history and careful analysis of the chest radiograph.

Soft but Powerful Artificial Muscles Based on 3D Graphene-CNT-Ni Heteronanostructures.

Bioinspired soft ionic actuators, which exhibit large strain and high durability under low input voltages, are regarded as prospective candidates for future soft electronics. However, due to the intrinsic drawback of weak blocking force, the feasible applications of soft ionic actuators are limited until now. An electroactive artificial muscle electro-chemomechanically reinforced with 3D graphene-carbon nanotube-nickel heteronanostructures (G-CNT-Ni) to improve blocking force and bending deformation of the ionic actuators is demonstrated. The G-CNT-Ni heteronanostructure, which provides an electrically conductive 3D network and sufficient contact area with mobile ions in the polymer electrolyte, is embedded as a nanofiller in both ionic polymer and conductive electrodes of the ionic actuators. An ionic exchangeable composite membrane consisting of Nafion, G-CNT-Ni and ionic liquid (IL) shows improved tensile modulus and strength of up to 166% and 98%, respectively, and increased ionic conductivity of 0.254 S m-1 . The ionic actuator exhibits enhanced actuation performances including three times larger bending deformation, 2.37 times higher blocking force, and 4 h durability. The electroactive artificial muscle electro-chemomechanically reinforced with 3D G-CNT-Ni heteronanostructures offers improvements over current soft ionic actuator technologies and can advance the practical engineering applications.